Zn(ii) anchored onto the magnetic natural hydroxyapatite (ZnII/HAP/Fe3O4): as a novel, green and recyclable catalyst for A3-coupling reaction towards propargylamine synthesis under solvent-free conditions

Article abstract of DOI:10.1039/c6ra20501a

In this paper, Zn(ii) anchored onto the magnetic natural hydroxyapatite (Zn^II/HAP/Fe₃O₄), as a new, versatile and magnetically recoverable catalyst, was prepared and characterized using different techniques such as FT-IR,

Full text of DOI:10.1039/c6ra20501a

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Zn (II) anchored onto the magnetic natural hydroxyapatite
(ZnII/HAP/Fe3O4): as a novel, green and recyclable catalyst for A3-
coupling reaction towards propargylamines synthesis under
solvent-free conditions
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Zeinab Zarei a and Batool Akhlaghinia*a
www.rsc.org/
In this paper, Zn(II) anchored onto the magnetic natural hydroxyapatite (ZnII/HAP/Fe3O4), as a new, versatile and
magnetically recoverable catalyst, was prepared and characterized using different techniques such as FT-IR, XRD, TGA,
TEM, EDX, VSM and ICP. The composition of this catalyst was determined and it was clearly found that the size of particles
was about 8-30 nm and rod-like in shape. Also, VSM analysis exhibited that the synthesized nanocatalyst had a
superparamagnetic behavior. The new nanocatalyst has been found to effectively catalyze the synthesis of structurally
different propargylamine derivatives via a one-pot three-component A3-coupling reaction of terminal alkynes, aldehydes
and secondary amines in high yields at 100 °C under solvent-free conditions. This green protocol provides significant
advantages, such as excellent yield of products, broad substrate scope, mild reaction conditions, minimization of chemical
waste, simple work-up procedure and environmentally benign and easy preparation of catalyst. Importantly, the prepared
nanocatalyst can be recovered by applying an external magnetic field and reused for seven cycles without significant loss
of activity.
and alkynes (A3- coupling).17 As multicomponent reactions (MCRs)
provide an elegant means to assemble molecular complexity and
1. Introduction
Owing to potent biological activities, propargylamines are an
attractive class of compounds. They can act as enzyme inhibitors,1
antitumor antibiotics,2 herbicides,3 and pharmaceutical agents.4
Moreover they are versatile structural elements and skeletons in
natural products4 and therapeutic drug molecules5 and also one of
diversity from simple and readily available starting materials via
simple and efficient one-step processes,18 the development of A3-
coupling reaction of an alkyne, aldehyde, and amine (which were
utilized to construct libraries of structurally complex compounds for
the evaluation of biological activities), is a continuing interest at the
forefront of synthetic organic chemistry.5a,19 However, in A3-
coupling reaction transition metal catalysts are necessary to fulfill
the reaction via formation of metal acetylide intermediate. A
number of homogeneous transition metal catalysts such as
Au(I)/Au(III) salts,20 Au(III) salen complexes,21a Au/CeO2,21b Au NPs,22
Cu(I) salts,23,24 CuBr,25 Cu(2-EH)2,26 Cu(OTf)2,27 Cu(I)/Cu(II)
complex,28 Cu(OAc)2,29 Cu(0),30 AgI salts,31 Fe(III) salts,32 Zn salts,33
Hg2Cl2,34 InCl3,35a InBr3,35b NiCl2,36 Ir complexes,37 Zr complex,38
AgOAc,39 Co(II),40 and a Cu/Ru(II) bimetallic system41 have been
used and proven effective in A3-coupling reactions. Additionally, to
remove the difficulties in recovering these expensive catalysts from
the reaction mixture which severely inhibit their wide use in
industry, reusable heterogeneous metal catalysts such as LDH-
AuCl4,42 Ag(I),43a AgTPA,43b Ag nanoparticles,43c Ag nanoparticles
supported by Ni,43d Cu(I) complexes,44a,44b CuCl,44c silica-immobilized
CuI,44d Ni-Y-zeolite,45 Zn dust,46 copper ferrite nanoparticles,47a
nanocrystalline copper(II) oxide,47bcopper-nanoparticles,30bCu/C
nanoparticles,47c impregnated copper on magnetite,47d copper–
zeolites,47e Fe3O4 nanoparticles,48 ferric hydrogensulfate,49 copper
the synthons for the synthesis of
compounds such as pyrrolidines,6a pyrroles,6b pyrrolophanes,7
aminoindolizines,8 isoindoline,9 imidazolidinones,10
2-
a variety of nitrogenous
aminoimidazoles11 and oxazolidinones.12 Thus, the development of
new synthetic methods for propargylamines has received great
attention from synthetic and medicinal chemists. In recent years,
various methods have been developed for the synthesis of these
compounds. Classical methods for the preparation of
propargylamines are as follows: (1) direct nucleophilic attack of
lithium acetylides or Grignard reagents to imines or their
derivatives;13,14 (2) direct C–C bond formation of terminal alkynes
with tertiary amines via C–H activation;15 (3) amination of
propargylic halides, propargylic phosphates, or propargylic
triflates;16 and (4) three-component coupling of aldehydes, amines,
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Scheme 2 Synthesis of different structurally propargylamines in the presence of ZnII/HAP/Fe3O4 under solvent-free conditions.
char on the bone, they were placed in an air furnace at 450 °C for
2. Experimental
2.1. General
8h which led to formation the bone ash (I). Then, the bone ash (I)
was burned at 800 °C for 5h to give a white powder that was
natural hydroxyapatite (II). 73
All chemical reagents and solvents were purchased from Merck and
Sigma-Aldrich chemical companies and were used as received
without further purification. The purity determinations of the
products were accomplished by TLC on silica gel polygram STL G/UV
254 plates. The FT-IR spectra were obtained using an AVATAR 370
FT-IR spectrometer (Therma Nicolet spectrometer, USA) using liquid
films (neat) on NaCl plates at room temperature in the range
between 4000 and 400 cm−1 with a resolution of 4 cm−1. The NMR
spectra were obtained in Brucker Avance 300 MHz instruments in
CDCl3. Mass spectra were recorded with a CH7A Varianmat Bremem
instrument at 70 eV electron impact ionization, in m/z (rel %).
Elemental analysis was performed using a Thermo Finnigan Flash EA
1112 Series instrument. TGA analysis was carried out on a Shimadzu
Thermogravimetric Analyzer (TG-50) in the temperature range of
25-900 °C at a heating rate of 10 °C min-1 under air atmosphere.
Transmission electron microscopy (TEM) was performed with a Leo
912 AB microscope (Zeiss, Germany) with an accelerating voltage of
120 kV and Transmission electron microscopy (TEM) with an
accelerating voltage of 150 kV was performed using TEM
microscope (Philips CM30). Inductively coupled plasma (ICP) was
carried out on a Varian, VISTA-PRO, CCD, Australia. Elemental
compositions were determined with an SC7620 Energy-dispersive X-
ray analysis (EDX) presenting a 133 eV resolution at 20 kV. The
magnetic property of catalyst was measured using a vibrating
sample magnetometer (VSM, 7400 Lake Shore). The crystal
structure of catalyst was analyzed by XRD using a D8 ADVANCE-
Bruker diffractometer operated at 40 kV and 30 mA utilizing Cu Kα
radiation (λ= 0.154 A°). All yields refer to isolated products after
purification by thin layer chromatography.
2.3. Preparation of magnetic HAP/Fe3O4 nanoparticles (III)
Into a 500-mL two-necked flask equipped with argon gas inlet tube,
a solution of FeCl3.6H2O (2.1 g, 8 mmol) and FeCl2.4H2O (1.05 g, 5.2
mmol) in 100 mL acetic acid (2%) was added. The resulting solution
was magnetically stirred for 30 min at room temperature, and then
natural hydroxyapatite (II) (4 g) was added into the solution and
vigorously stirred for 12h to obtain a homogenous brick solution.
Then the resulting mixture was quickly poured into NaOH solution
(100 mL, 5%) in one portion and soaked under argon atmosphere at
room temperature. After soaking for 12h, the synthesized
HAP/Fe3O4 nanoparticles (III) (as a brown powder) was collected by
an external magnet, washed with distilled water (4×100 mL) until
the pH reached 7, and then dried at ambient temperature.
2.4. Preparation of ZnII/HAP/Fe3O4 nanoparticles (IV)
To a solution of Zn(OAc)2.2H2O (1.4 g, 6 mmol) in absolute ethanol
(25 mL), the synthesized HAP/Fe3O4 nanoparticles (III) (2 g) was
added and the reaction mixture was refluxed for 24h. Subsequently,
the resulting suspension was magnetically separated, washed
repeatedly with water (2 × 100 mL) and dried at 60 °C for 12h.
2.5. Typical procedure for preparation of 4-(1,3-diphenylprop-2-
ynyl)morpholine (4a)
A mixture of benzaldehyde (0.1 g, 1 mmol), morpholine (0.08 g, 1
mmol), phenylacetylene (0.10 g, 1 mmol) and ZnII/HAP/Fe3O4 (IV)
(0.08 g, 8 mol%) was taken into a round-bottomed flask and stirred
at 110 °C. The progress of reaction was monitored by TLC (n-
hexane: EtOAc, 1:1). After completion of the reaction, the
nanocatalyst was separated with an external magnet and the
reaction mixture was extracted with water (2 × 10 mL) and ethyl
acetate (2 × 10 mL). The organic layer was evaporated and the
resulting crude product was purified by thin layer chromatography
2.2. Extraction of natural hydroxyapatite from cow bones
Natural hydroxyapatite was obtained in two-stage calcination
processes from the cow bones as the raw material. In the first step,
the cow bones were cleaned by washing with hot water several
times to remove oily materials. In order to remove the remaining
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using ethyl acetate / n-hexane (1/1) as eluent to give the desired due to the use of argon atmosphere in the soaking process, no
product. The pure 4-(1,3-Diphenylprop-2-ynyl) morpholine was diffraction peak of Fe2O3 NPs was detected in the structure of the
obtained with a 95% yield (0.25 g).
synthesized catalyst. Also, there is no obvious characteristic
diffraction peaks associated to Zn(OH)2 formation.79
3. Results and Discussion
Also the TEM images presented in Fig. 3a and 3b showed the size
of particles was in the range of 8-30 nm with rod-like in shape.80
Moreover, the images clearly show the entrapment of the Fe3O4
particles in the natural hydroxyapatite matrix which resulted from
agglomeration of small particles and good dispersity of Fe3O4 NP
into the HAP scaffold. Likewise, in the TEM analysis with higher
voltage (150 kV), the dark particles can be distinguished from the
usual brighter ones (Fig. 3c and 3d). Due to the stronger absorption
contrast, it is clear that the dark particles are identified as iron
phase (Fe3O4), whereas the phase containing more (brightness)
pores is HAP.
3.1. Characterization of catalyst
Zn (II) anchored onto magnetic natural hydroxyapatite
(ZnII/HAP/Fe3O4) was synthesized according to the pathway shown
in Scheme 1 as a novel, efficient and reusable heterogeneous
catalyst. This newly synthesized catalyst was fully characterized by
different techniques such as Fourier transform infrared
spectroscopy
(FT-IR),
thermogravimetric
analysis
(TGA),
transmission electron microscopy (TEM), energy-dispersive X-ray
analysis (EDX), vibrating sample magnetometer (VSM), X-ray
powder diffraction (XRD) and inductively coupled plasma (ICP). The
results obtained from these techniques, confirmed the successful
preparation of the new nanocatalyst.
Furthermore, energy dispersive spectrometer (EDS) revealed the
existence of Ca, P, O, Fe and Zn elements in nanocatalyst as shown
in Fig. 4. It is clear that zinc was successfully anchored onto the
magnetic hydroxyapatite matrix due to the considerable intensity of
Zn (II). In addition, there are no impurity elements in the
nanocatalyst structure.
The FT-IR spectra of the bone ash (I), HAP (II), HAP/Fe3O4 (III) and
ZnII/HAP/Fe3O4 (IV) were illustrated in Fig. 1(a-d). As can be seen in
Fig. 1 a (FT-IR spectrum of I) the relatively broad band around 3660-
3280 cm-1 attributed to the asymmetric and symmetric stretching
vibrations of the hydroxyl groups in the bone ash matrix.73 An
absorption band at 1629 cm-1 was indicative of amide functional
groups of the protein constituents in the organic matrix of bone
ash.74 Also, the observed band at 1471cm-1 with a shoulder at 1420
cm-1 could be ascribed to the stretching vibration of carbonate
ions.74 Furthermore, the absorption bands appearing at 1039, 961,
605, 562 cm-1 were related to the stretching vibration modes of
phosphate groups.74 After heat treating of the bone ash at 800 °C,
the broad band (3660-3280 cm-1) was disappeared and replaced by
a weak and sharp absorption band at 3571 cm-1 which is due to the
hydroxyl stretching vibration. (Fig. 1 b).74 This is in agreement with
the change of color from black powder ash (I) to a white powder
(II). The FT-IR spectrum of HAP/Fe3O4 (III) (Fig. 1 c) showed a broad
band at 3415 cm-1 that revealed the presence of hydroxyl groups on
the surface of the magnetic nanoparticles.75 It is worth noting that
the stretching vibration bands of Fe-O bonds at around 633-565 cm-
Fig. 1 FT-IR spectrum of (a) the bone ash(I), (b) HAP(II), (c)
HAP/Fe3O4 (III), (d) ZnII/HAP/Fe3O4 (IV) and 7th reused
ZnII/HAP/Fe3O4.
1
were covered by the broad stretching vibration bands of
phosphate groups of hydroxyapatite which cannot be
distinguished.73 Also, the coordination of Zn(OAc)2.2H2O was
confirmed by decreasing the intensities of absorption bands of
hydroxyl groups (Fig. 1 d).
The crystal structure of the obtained HAP and ZnII/HAP/Fe3O4
were characterized by XRD. As seen in Fig. 2a, the XRD pattern
exhibited reflection peaks at around 2Ɵ = 26.0°, 32.0°, 33.1°, 34.2°,
40.0°, 46.7° and 49.5° that can be indexed to (002), (211), (300),
(202), (130), (222) and (213) planes of hexagonal structure of the
natural hydroxyapatite (JCPDS: 24-0033).76,77 The strong peaks
indicated phase purity of HAP nanoparticles. Moreover, in
comparison with the pattern of the natural hydroxyapatite, Fig. 2b
showed several additional peaks at 2Ɵ = 35.4°, 43.3°, 53.7°, 57.3°
and 62.9° which assigned to the (311), (400), (422), (511) and (440)
crystal planes, respectively, in Fe3O4 cubic lattice (JCPDS: 19-
0629).78 According to the Deby-Scherer equation, the crystallite size
of ZnII/HAP/Fe3O4 was estimated to be 30 nm. It is noteworthy that
Fig. 2 The XRD patterns of (a) HAP and (b) ZnII/HAP/Fe3O4.
4 | J. Name., 2012, 00, 1-3
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Fig. 4 The EDS analysis of ZnII/HAP/Fe3O4.
Fig. 3 TEM images with 120 kV (a, b) and 150 kV (c, d) of
ZnII/HAP/Fe3O4.
The magnetic behaviour of the nanocatalyst was measured using a
vibrational sampling magnetometer (VSM) at room temperature. As
can be seen in Fig. 5, the hysteresis loop of ZnII/HAP/Fe3O4 was
Fig. 5 Magnetization curve of ZnII/HAP/Fe3O4.
completely reversible which indicated
a superparamagnetic
behaviour. Also, the curve indicated that the saturation
magnetization value of ZnII/HAP/Fe3O4 was about 7.90 emu/g which
was lower than the reference value for bulk Fe3O4 particles (Ms= 73
emu/g).81 This phenomenon can be attributed to the placement of
Fe3O4 nanoparticles into the HAP matrix. However, compared to the
previously published report,73 the magnetization value of this
catalyst was almost doubled due to using argon atmosphere in the
soaking process resulting in Fe3O4 NPs preparation method. These
magnetic properties were high enough for magnetic separation of
the nanocatalyst from the reaction mixture with an external
magnet.
Thermogravimetric analysis (TGA) of ZnII/HAP/Fe3O4 was also
performed to investigate the thermal stability of the catalyst. As it is
obvious in Fig. 6, TGA thermogram showed three major weight-loss
stages. The first stage was mainly related to the evaporation of
absorbed physical and chemical water on the catalyst surface
(weight loss 0.79% at 32-140 °C). The second one which was
occurred at 140-450 °C (weigh loss 2.99%), was corresponded to the
removal of the organic segments in the structure of III. After that,
there was a weight loss of about 0.33% ranging from 450 °C to 750
°C due to the decomposition of calcium carbonate to calcium oxide
which verified the presence of natural hydroxyapatite.74
Fig. 6 TGA thermogram of ZnII/HAP/Fe3O4.
Besides, the total zinc content in the freshly prepared catalyst
which was determined by ICP analysis is calculated to be 66957
ppm, 0.06 gr or 1.02 mmol of Zn (II) per 1.00 g of nanocatalyst.
3.2. Catalytic synthesis of propargylamines
To develop an improved catalytic system for the synthesis of
propargylamines, a series of experiments were carried out by A3-
coupling reaction between benzaldehyde, morpholine and
phenylacetylene and the results are summarized in Table 1. Low
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yield of product was produced in the absence of any catalyst as the benzaldehyde/ phenylacetylene
Journal Name
/
morpholine) generated the
same as in the presence of Fe3O4 NPs, HAP (II) and HAP/Fe3O4 (III), desired A3- product in 95% isolated yield (Table 1, entry 17). Lower
while ZnII/HAP/Fe3O4 nanoparticles afforded excellent yield (Table catalyst loading (Below 8 mol% ) resulted lower conversion while
1, entries 1-5). In solvent-free condition, ZnII/HAP/Fe3O4 additional amounts of catalyst (9 mol % and 10 mol %) have not any
nanoparticles catalyzed A3-coupling reaction as well as in toluene considerable effects on the reaction yield and reaction rate. In the
(compare entry 6 with entry 5). Having found the most effective presence of the optimized amount of Zn(OAc)2.2H2O (8 mol%
catalyst (ZnII/HAP/Fe3O4 nanoparticles in solvent-free condition at Zn(II)), the A3-coupling reaction of benzaldehyde, morpholine and
110 °C in terms of yield, cost effectiveness and reaction time), we phenylacetylene is completed after 7h (Table 1, entry 18).
address next optimization in terms of catalyst loading, temperature, Therefore, we may conclude that Zn(II) anchored onto the surface
solvent screening
and molar ratio of benzaldehyde/ of HAP/Fe3O4 increases the catalytic activity as well as providing
phenylacetylene/ morpholine (Table 1,entries 7- 17). In the optimal easy separation of catalyst from the reaction mixture by an external
process, 8 mol % of ZnII/HAP/Fe3O4 nanoparticles (in solvent-free magnet.
condition at 110 °C and by applying 1/1/1 molar ratio of
Table 1 Optimization of various reaction parameters for the synthesis of 4-(1,3-diphenylprop-2-ynyl)morpholine in
the presence of ZnII/HAP/Fe3O4.
O
N
O
O
H
+ Ph
H
+
N
Ph
Catalyst
(mol %)
Temperature
( °C )
Time
(h)
Isolated Yield
(%)
Entry
Solvent
Molar ratio of (benzaldehyde/
phenylacetylene/ morpholine)
1
2a
3b
4c
5
1/1.1/1
1/1.1/1
1/1.1/1
1/1.1/1
1/1.1/1
1/1.1/1
1/1.1/1
1/1.1/1
1/1.1/1
1/1.1/1
1/1.1/1
1/1.1/1
1/1.1/1
1/1.1/1
1/1.1/1
1/1.1/1
1/1.1/1
-
toluene
110
110
4/24
10/10
10/10
10/10
10/10
95
0.05(g)
toluene
4/24
0.05(g)
toluene
110
4/24
0.05 (g)
toluene
110
4/24
4
5
5
toluene
110
6
-
110
4
95
7
6
-
110
3
80
8
7
-
110
3
85
9
8
-
110
3
95
10
11
12
13
14
15
14
15
9
-
-
110
3
95
10
8
110
3
95
-
100
3
80
8
H2O
PEG
DCM
THF
1,4-
dioxane
CH3CN
-
reflux
110
3
10
8
3
30
8
reflux
reflux
reflux
3
5
8
3
5
8
3
0
16
17
18d
1/1.1/1
1/1/1
8
8
8
reflux
110
3
3
7
20
95
95
1/1/1
-
110
aThe reaction was performed in the presence of Fe3O4 NP.b The reaction was performed in the presence of HAP
(II).c The reaction was performed in the presence of HAP/Fe3O4(III).d The reaction was performed in the presence
of Zn(OAc)2.2H2O.
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On the basis of the optimized reaction conditions in hand (Table1, in 80% isolated yield even after a long period of time (Table 2, entry
entry 17), the scope and generality of the A3-coupling reaction were 12). In addition, electronic effects on phenylacetylene were
investigated by employing a variety of terminal alkynes, secondary investigated and it was seen that phenylacetylenes bearing
amines and aldehydes with a wide range of functional groups to electron-rich groups / or electron-deficient groups produced the
find the effectiveness of the ZnII/HAP/Fe3O4 nanocatalyst. The desired propargylamines in good /or moderate yields, which was
results are summarized in Table 2. As depicted in Table 2, when probably due to the nucleophilicity power of the acetylide anion
phenyacetylene, morpholine and benzaldehyde were used as the (see Scheme 3 and Table 2, entries 13-14 and 23-24). Interestingly,
starting substrates, the desired propargylamine was formed with an in all cases, when pyrrollidine was applied as a secondary amine
excellent yield (Table 2, entry 1), whereas the benzaldehydes under the identical conditions, the products were obtained in lower
bearing electron-withdrawing groups (such as fluoro, chloro and yields or in longer reaction times (Table 2, entries 15-24), which
bromo) afforded the desired products 4b-4f in 80-90% isolated may be attributed to low stability of corresponding imminium ion.82
yields in longer reaction times (Table 2, entries 2-6). On the other It is important to note that aliphatic aldehydes (such as
hand, benzaldehydes bearing electron-donating groups (such as formaldehyde, cinnamaldehyde, 3-methyl butanaldehyde and 3-
methyl, hydroxyl and methoxy) afforded the corresponding methyl pantaldehyde) and secondary aliphatic amines such as
products in good to excellent yields in shorter reaction times (Table piperidine and piperazine did not afford the corresponding product
2, entries 7-10). These results can be attributed to the stability of under the same reaction conditions. These results indicate the
corresponding iminium ion which markedly affect on the reaction superior properties of ZnII/HAP/Fe3O4 nanocatalyst for the synthesis
rate (see Scheme 3). Also, 1-naphthaldehyde underwent A3-coupling of structurally different propargylamines and also the selectivity of
reaction with moderate rate (Table 2, entry 11). By using the present methodology in A3-coupling reaction of aromatic
heteroaromatic aldehydes such as thiophene-2-carboxaldehyde, aldehydes, morpholine and pyrrolidine.
the reaction led to formation of the corresponding propargylamine
Table 2 Synthesis of different structurally propargylamines in the presence of ZnII/HAP/Fe3O4 under solvent-free
condition.
R2
ZnII/HAP/Fe3O4 (8 mol%)
H + R3
H
R1CHO + R2
R1
Solvent-free, 110 °C
1
2
3
4a-x
R3
Entry
R1
Amine (R2)
R3
Product
Time
Isolated Yield
(h)
(%)
95
1
2
C6H5
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
Morpholine
C6H5
C6H5
4a
4b
4c
4d
4e
4f
3
4-FC6H4
7
80
3
4-ClC6H4
2-ClC6H4
4-BrC6H4
3-BrC6H4
4-MeC6H4
3-MeC6H4
2-HOC6H4
C6H5
C6H5
C6H5
6
90
4
7
90
5
6
90
6
C6H5
C6H5
C6H5
6
85
7
4g
4h
4i
2
97
8
2
95
9
C6H5
C6H5
C6H5
4
1
90
10
11
12
13
4-MeOC6H4
1-Naphthal
2-Thienyl
C6H5
4j
95
4k
4l
12
65
C6H5
4-ClC6H4
11/24
4
80/80
70
4m
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14
15
16
17
18
19
20
21
22
23
24
C6H5
C6H5
Morpholine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
Pyrrolidine
4-t-BuC6H4
C6H5
4n
4o
4p
4q
4r
2
3
95
90
60
80
80
85
95
90
95
60
90
4-FC6H4
4-ClC6H4
2-ClC6H4
4-BrC6H4
4-MeC6H4
3-MeC6H4
4-MeOC6H4
C6H5
C6H5
8
C6H5
6
C6H5
7
C6H5
4s
6
C6H5
4t
2
C6H5
4u
4v
4w
4x
2
C6H5
2.5
6
4-ClC6H4
4-t-BuC6H4
C6H5
2.5
Most of the obtained propargylamines (4a-g, 4i-l, 4o-4q and 4s-v) Based on the reports in the literature33b and our experimental
were known and characterized by comparing their physical data results, a plausible mechanism of A3-coupling reaction catalyzed by
(colour) and spectral data (mass spectrometry) with those of ZnII/HAP/Fe3O4 is shown in Scheme 3. At first, the terminal alkynes
authentic samples reported in the literature. The structure of the are coordinated to Zn(II) anchored onto HAP/Fe3O4 producing the
selected products was further identified by FT-IR, 1HNMR and alkyne complex I. Then, ZnII/HAP/Fe3O4 inserted into the C-H bond
13CNMR spectroscopy. The novel synthesized compounds (4h, 4m, of terminal alkynes to give the acetylide complex II on the surface
4n, 4r, 4w and 4x) were also characterized by using elemental of the nanocatalyst. In the third step, deporotonation of the
analysis technique. The progress of the reaction was monitored by acetylide complex II generates the zinc acetylide intermediate III,
disappearance of starting materials and formation of product on which intracts with the imminium ions (generated from aldehyde
TLC which confirmed the completion of the reaction. In the FT-IR and secondary amine) and affords the intermediate IV. It is worth
spectra of the synthesized products, disappearance of the following noting that the presence of ZnII/HAP/Fe3O4 accelerates the
bands, a strong absorption band at 1703 cm-1 (related to the C=O formation of imminium salt through the coordination of the
stretching vibration of aldehyde), a broad band at 3334-3302 cm-1 carbonyl group of aldehyde to Zn(II). Subsequently, nucleophilic
(due to the N-H stretching vibration of morpholine)/or a sharp band attack of acetylide ion to imminium carbon results the final desired
at 3000 cm-1 (due to the N-H stretching vibration of pyrollidine), a product V. In the following, ZnII/HAP/Fe3O4 is released from the
strong band at 3300 cm-1 (due to the ≡C–H stretching vibration), product for further cycle of reactions. With respect to the fact that
and replacing a sharp band at 2200-2100 cm-1 (due to the C≡C aldehydes bearing electron-donating substituents react faster than
stretching vibration of terminal acetylene) by
a very weak aldehydes substituted with electron-withdrawing groups (because
absorption band at 2230-2103 cm-1 (due to the C≡C stretching of formation more stable imminium ion, see Table 2, entries 7-10
vibration of propargylamine), were the evidences of and 20-22) it is speculated that the formation of the imminium ion
propargylamines formation. Also, in NMR, the methine proton and can be one of the rate-determining steps of the A3-coupling
carbon (CH) were appeared at 5.34-4.69 and 60.07-49.9 ppm reaction. Further studies to elucidate the mechanism are currently
respectively.
underway in our laboratory.
8 | J. Name., 2012, 00, 1-3
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R2
R3
N
OH
II
HO
H
Zn
OAc
AcO
O
R1
R2
H
R3
II OH
Zn
HO
OH
II
HO
Zn
N
H
OAc
AcO
OAc
AcO
O
R2
OH
R1
R1
H
H
N
R3
O
II OH
Zn
HO
R1
H
R2
R1
R3
H
OAc
AcO
+
N
. OH
HOAc
II OH
HO
AcO
Ar
III
OH
HO
Zn
OH
II
HO
AcO
OAc
Ar
AcO
R3
H
H
II
+
N
. OH
Ar
R2
R1
IV
HOAc
OH
HO
OH
OAc
II
Zn
HO
AcO
Ar
AcO
Ar
R3
H
H
+
N
I
R2
R1
OH
Ar
H
II
Zn
HO
AcO
OAc
R2
R1
R3
R1= Aryl
R2 , R3= Alkyl
N
Ar = C6H5, 4-ClC6H4, 4-t-BuC6H4
Ar
Fe3O4
HAP
=
=
V
Scheme 3 Proposed reaction mechanism for the synthesis of propargylamines in the presence of ZnII/HAP/Fe3O4.
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To investigate the heterogeneous nature of ZnII/HAP/Fe3O4 indicates that 93% of Zn (II) could be found in the structure of the
nanocatalyst, the hot filtration test has been carried out on model catalyst after seven runs.
reaction under the optimized condition. In this test, a mixture of
ZnII/HAP/Fe3O4 (0.08 g, 8 mol%), phenylacetylene (0.10 g, 1 mmol),
morpholine (0.08 g, 1 mmol) and benzaldehyde (0.1 g, 1 mmol) was
heated at 110 °C under solvent-free condition for 1.5h. After 50 %
conversion, the catalyst was magnetically separated from the
reaction mixture and then the reaction was continued for an
additional time (1.5h). No further product formation was observed
which was monitored by TLC. This result clearly demonstrates that
no leaching of Zn(II) took place during the reaction, and
ZnII/HAP/Fe3O4 is truly heterogeneous in nature.
Fig. 7 Synthesis of 4-(1, 3-Diphenylprop-2-ynyl) morpholine in the
The reusability of the catalyst is one of the main advantages for
presence of reused ZnII/HAP/Fe3O4.
commercial applications. Thus, to determine the reusability of the
prepared nanocatalyst, after completion of the model reaction, the
To show the efficiency of ZnII/HAP/Fe3O4 over some of the reported
reaction mixture was diluted with ethyl acetate, the catalyst was
magnetically separated and then washed with water (20 mL), and
catalysts in the literature, we compared the catalytic performance
boiled ethyl acetate (20 mL) for several times to remove the
of ZnII/HAP/Fe3O4 in the synthesis of 4-(1,3-diphenylprop-2-yn-1-yl)
residual of organic compounds. Then the nanocatalyst was dried at
morpholine with various catalysts (Table 3). As is shown in Table 3,
60 °C for 12h and used for subsequent runs under the same
some of these methods suffer from one or more of the following
reaction conditions. The catalytic activity of the catalyst was
drawbacks, such as requiring long reaction time to achieve the
remained without any noteworthy loss of activity for seven
reasonable yield (Table 3, entries 1-3), using toxic solvents (Table 3,
successive runs as it can be seen in Fig. 7. The excellent catalytic
entries 4-11), and homogenous catalysts (Table 3, 12-19) and
activity of the nanocatalyst during the recovery process have been
moreover, a difficult process to separate heterogeneous catalysts
verified by these results. Also, as can be seen in Fig. 1e, the shape of
by filtration, or centrifugation (Table 3, 20-23). Therefore, using
ZnII/HAP/Fe3O4 as an efficient and green nanomagnetic catalyst can
the characteristic peaks were well preserved and no significant
change was occurred in the structure of the nanocatalyst after
remove these drawbacks; in addition, it can be easily separated
repeated cycles of the reaction. ICP analysis showed that freshly
from the reaction mixture by an external magnet. These results
prepared catalyst contains 66957 ppm, 0.066 g or 1.02 mmol of Zn
(II) per 1 g of the catalyst, while the 7th reused catalyst contains
in the literature.
61788 ppm, 0.061 g or 0.94 mmol of Zn (II) per 1 g of the catalyst. It
proved that our method is superior to the other previous methods
Table 3 Comparison between efficiency of ZnII/HAP/Fe3O4 and some other catalysts for the synthesis of 4-(1,3-
diphenylprop-2-ynyl) morpholine.
Entry
Catalyst (mol%)
Molar
ratio*
solvent
Temp
(°C)
100
100
90
Time (h)
Yield
(%)
83
Ref
1
2
3
Au/CeO2, Au/ZrO2 (0.10 g)
Au@GO (1)
1/1.2/1.3
1/1.2/1.3
1/2/3
H2O
H2O
12
18
24
21b
83
90
Fe3O4 NPs/GO-CuONPs
(0.02 g)
EtOH
87
54
4
5
6
7
8
Fe3O4@SBA-15 (5)
Cu(OH)-Fe3O4 (3)
CuFe2O4 (6.50)
1/1.2/1.5
toluene
toluene
toluene
toluene
toluene
110
120
80
8
3
4
4
3
72
99
85
92
90
51
47d
47a
50a
84
1/1.2/1.3
1/1.1/1.2
1/1/1.2
Cu(I)-N2S2**-salen (3)
Cu0-Mont (0.05)
80
110
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9
CuO (10)
[Cu(N2S2)]Cl@Y-zeolite
(0.68 g)
1/1.3/1.5
1/1.1/1.2
toluene
DCE
90
70
8
65
90
47b
44b
10
12
11
12
13
14
15
16
17
18
19
20
21
22
23
24
CuHAP (0.10 g)
NiCl2 (10)
1/1.2/1.3
1/1.2/1.5
1/1.3/1.5
1/1.2/1.5
1/1.2/1.5
1/1.2/1.5
1/1.1/1.1
1//1/1
CH3CN
toluene
reflux
111
reflux
120
100
100
100
80
6
70
88
96
95
92
98
96
44
90
85
95
95
91
95
44a
36
8
Zn(OAc)2.2H2O (15)
CuCN (2)
toluene
7
33b
24d
24b
24c
85
[bmim]PF6
PEG
2
CuI (10)
12
CuI (3)
toluene
6
[AQ2Cu(II)](5)
Cu[(CH3CN)n(PPh3)]Br (5)
CuPy2Cl2 (1)
Solvent-free
toluene
70 ***
85
28c
86
1/1.5/1.5
1/1.2/1.5
1/1/1
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
95
40***
Cu(salen) (3)
80
2.5
2
28a
55
ZnO (10)
100
100
70
Cu2O/ZnO (0.01 g)
CuNPs/TiO2 (0.50)
ZnII/HAP/Fe3O4 (8)
1/1.2/1.5
1/1/1
1
61
7
57
1/1/1
110
3
Present
study
* Molar ratio of (aldehyde/amine/alkyne). **Bis[2-(phenylthio)benzylidene]-1,2-ethylenediamine.*** minute.
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EDX, VSM and ICP techniques. Characterization results revealed
that the size of particles was about 8-30 nm, rod-like in shape, and
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a
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secondary amines with high yields in green media without requiring
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12 | J. Name., 2012, 00, 1-3
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